Considerable disagreement exists in the literature as to the opinion of neonatologists as to the perception of pain by neonates and the efficacy and safety of drugs to alleviate pain. Therefore in may cases a surgical procedure would be carried out without pain altering drugs. A comparison of surveys carried out in the early 1980s with one completed this past year, show that now more physicians believe infants perceive pain and therefore the use of pain altering drugs in infants is increasing. Still a significant portion of them believe that pain is not perceived in infants and that this is probably the result of a less well developed brain. We propose the first specific aim of this project which is to compare pain sensitivity in neonates and adults to determine whether neonatal animals do perceive pain with the similarity as young adults. Some effort will be spent in the adoption of methodology such as the stretching test, hot plate and when appropriate the tail flick test for measurement of pain in the neonate. Although some work has been done in this area a well controlled comparative study using classical endpoints for pain has not appeared. The concern about the safety of the opiates and other drugs which was expressed by a number of physicians in the most recent survey prompted the next two aims; namely, a comparative study of the efficacy of the drugs and an evaluation of the rate of onset and degree of tolerance and physical dependence in the neonate. Our laboratory has extensive experience in studying these phenomena in young adults. Again, methodology development will be important in accomplishing this specific aim. We further hypothesize that the development of the opiate receptor and endogenous opioid systems of the brain are correlated with the ability of the neonate to perceive pain and the efficacy of the opiates to alleviate pain. These last two specific aims will be carried out in neonates only since considerable information is available in the literature as to receptor function and endogenous opioids in adults. Again data on the development of the receptors and the endogenous peptides exists in the literature but they have not been correlated with the onset of pain sensitivity and opiate efficacy. This project has significant theoretical and practical importance since the marked stress that a neonate would experience from a painful stimulus without proper treatment could have deleterious effects in later life.